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鼻腔给予锰对大鼠神经传递和空间学习的影响。

Effect of intranasal manganese administration on neurotransmission and spatial learning in rats.

机构信息

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmieście 26/28, 00-927 Warsaw, Poland.

出版信息

Toxicol Appl Pharmacol. 2012 Nov 15;265(1):1-9. doi: 10.1016/j.taap.2012.09.015. Epub 2012 Sep 27.

DOI:10.1016/j.taap.2012.09.015
PMID:23022103
Abstract

The effect of intranasal manganese chloride (MnCl(2)·4H(2)O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2weeks MnCl(2)·4H(2)O at two doses the following: 0.2mg/kg b.w. (Mn0.2) or 0.8mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions.

摘要

鼻腔内氯化锰(MnCl(2)·4H(2)O)暴露对成年大鼠空间学习、记忆和运动活动的影响,在 Morris 水迷宫任务中进行了评估。3 月龄雄性 Wistar 大鼠每天接受以下两种剂量的 MnCl(2)·4H(2)O 2 周:0.2mg/kg b.w.(Mn0.2)或 0.8mg/kg b.w.(Mn0.8)。对照组(Con)和锰暴露组观察在水迷宫中的行为表现和学习。重复测量方差分析(ANOVA)显示,两组在水迷宫中的获得性无显著差异。然而,在第 5 天的探测试验中,结果显示出锰处理后空间记忆缺陷。行为实验完成后,通过 HPLC 在选定的脑区(前额叶皮层、海马体和纹状体)中测定神经递质及其代谢物的区域脑浓度。方差分析显示,与对照组相比,治疗组的单胺类和代谢物含量存在显著差异。在探测试验中,在前东南象限(SE)平台位置上穿越平台的次数与神经递质周转率之间存在负相关,这表明锰(Mn)处理后空间记忆和认知表现的损害与大脑中 5-羟色胺能、去甲肾上腺素能和多巴胺能神经传递的调节有关。这些发现表明,鼻腔内应用 Mn 可损害空间记忆,并导致多个脑区中单胺类物质的组织水平和代谢发生显著变化。

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